Excessive mitochondrial fission has been implicated in the etiology of neuronal cell death in traumatic brain injury (TBI). In the present study, we examined the efficacy of melatonin (Mel) as a neuroprotective agent against TBI-induced oxidative damage and mitochondrial dysfunction. We assessed the impact of Mel post-treatment (10 mg/kg b.wt., i.p.) at different time intervals in TBI-subjected Wistar rats. We found that the Mel treatment significantly attenuated brain edema, oxidative damage, mitochondrial fission, and promoted mitochondrial fusion. Additionally, Mel-treated rats showed restoration of mitochondrial membrane potential and oxidative phosphorylation with a concomitant reduction in cytochrome-c release. Further, Mel treatment significantly inhibited the translocation of Bax and Drp1 proteins to mitochondria in TBI-subjected rats. The restorative role of Mel treatment in TBI rats was supported by the mitochondrial ultra-structural analysis, which showed activation of mitochondrial fusion mechanism. Mel enhanced mitochondrial biogenesis by upregulation of PGC-1α protein. Our results demonstrated the remedial role of Mel in ameliorating mitochondrial dysfunctions that are modulated in TBI-subjected rats and provided support for mitochondrial-mediated neuroprotection as a putative therapeutic agent in the brain trauma.

过度的线粒体裂变与创伤性脑损伤 (TBI) 中神经元细胞死亡的病因有关。在本研究中，我们检查了褪黑激素 (Mel) 作为神经保护剂对抗 TBI 诱导的氧化损伤和线粒体功能障碍的功效。我们评估了 Mel 后处理的影响（10 mg/kg b.wt.，ip) 在 TBI 受试者的 Wistar 大鼠中以不同的时间间隔。我们发现 Mel 治疗显着减轻了脑水肿、氧化损伤、线粒体裂变，并促进了线粒体融合。此外，Mel 治疗的大鼠表现出线粒体膜电位和氧化磷酸化的恢复，同时细胞色素-c 的释放减少。此外，Mel 治疗显着抑制了 TBI 大鼠中 Bax 和 Drp1 蛋白向线粒体的易位。Mel治疗对TBI大鼠的修复作用得到了线粒体超微结构分析的支持，表明线粒体融合机制被激活。Mel通过上调PGC-1α蛋白增强线粒体生物发生。